KEYWORDS 2 cardiovascular disease, mortality, non-alcoholic fatty liver disease, fatty liver index 3 Abstract Background Despite the known association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD), it remains uncertain whether NAFLD predicts future CVD events, especially CVD mortality. We evaluated the relationship between fatty liver index (FLI), a validated marker of NAFLD, and risk of major adverse cardiac events (MACE) in a large population-based study.Methods We identified 3,011,588 subjects without a history of CVD who underwent health examinations from 2009 to 2011 in the Korean National Health Insurance System cohort. The primary endpoint was a composite of cardiovascular deaths, non-fatal myocardial infarction (MI), and ischemic stroke. Cox proportional hazards regression analysis was performed to assess the independent association between FLI and the primary endpoint.Results During the median follow-up of 6 years, there were 46,010 cases of MACE (7,148 cases of cardiovascular death, 16,574 non-fatal MI, and 22,228 ischemic stroke). There was a linear association between higher FLI values and higher incidence of the primary endpoint. In the multivariable models adjusted for factors including body weight and cholesterol levels, the hazard ratio (95% CIs) for the primary endpoint comparing the highest vs. lowest quartiles of FLI was 1.99(1.91-2.07). The corresponding odds ratios (95% CIs) for cardiovascular death, non-fetal MI, and ischemic stroke were 1.98 (1.9-2.06), 2.16 (2.01-2.31), and 2.01 (1.90-2.13), respectively. The results were similar when we stratified analysis by age, sex, dyslipidemia medication, obesity, diabetes, and hypertension.Conclusions Our findings indicate that FLI, a surrogate marker of NAFLD, has prognostic value for